Battle Against Drug Addiction Must Be Waged From Better Financed Laboratories

The "war on drugs" will not be won in the jungles of Colombia or along the borders of the United States. Drug abuse will come under control when we, as scientists, find ways to relieve addicts of their compulsive need for a fix. Addictions are chronic diseases originating in adolescence and young adulthood. Although the decision to experiment with drugs may have been voluntary, what occurs thereafter is a physiological disorder, not a "failure of will." Susceptibility to addiction is an inherent characteristic that has been demonstrated in every species of animal tested. In humans, for example, cocaine activates the brain's intrinsic reward system, initially producing an intense sense of pleasure, a "high." It also acts as a reinforcer - an inducer of long-term memory - that creates a neurobehavioral demand for cocaine, resulting in "drug-seeking behavior." The reinforcing properties of crack (a smokable and quickly absorbed form of cocaine) are so powerful that a single dose may create an addict, and long drug-free periods will not extinguish the craving. Scientifically speaking, the study of addiction is analogous to the study of the molecular basis of learning and of developmental differentiation, which have been subject to astonishing recent progress focusing on signaling mechanisms. For example, recombinant DNA technology has made possible the cloning and structural characterization of most hormone and neurotransmitter receptors, the adenylyl cyclase and phosphoinositide signal transduction systems, and the serine-threonine and tyrosine kinases that have elucidated short-term signaling. Study of simple neural networks like aplysia have also shed light on intermediate-term cellular changes, and studies of long-term synaptic potentiation and Ca2+ cycling have begun to clarify functional changes related to memory. Mapping of brain organization provides the expectation of functional characterization of limbic system structures and connections. The chemical signals responsible for sequential transcription of different genetic elements during differentiation may be analogous to those establishing drug-induced reinforcement. While research into addiction has yielded the structure of the nicotine receptor, the dopamine reuptake inhibition theory of cocaine action, and many features of the opioid system, the full force of contemporary science has not been applied to the problem. There are several reasons for this. One is the conviction that addiction is a behavioral disorder and should be treated as such, not by "more drugs." Another is the belief that addicts are weak-willed, morally suspect, self-destructive and undeserving. A third reason is the extremely low funding levels for biological research into addiction. This has hampered recruitment of scientists, especially those with molecular or cellular biology expertise. There has been no national mandate for biological research on drug abuse, and unfortunately none is proposed. Ten years of a well-funded commitment - beginning at $200 million and increasing to $500 million over five years - should decipher the detailed mechanisms underlying each of the principal addictions and provide effective therapy to large numbers of victims. It should prepare us to deal effectively with new drugs of abuse as they surface. We are not starting from scratch in this effort. There are good animal models of addiction to study. The reward center in the nucleus accumbens has been identified in many species. Activating and inhibitory analogs of many neurotransmitters and addicting agents are available for experimentation. Research results on one substance of abuse may apply to others. Large groups of patients eager to break their habit await therapeutic trials. There is good reason to believe that long before a full comprehension of the addictive process is achieved, effective therapies will be discovered. Three research groups have already proposed promising candidates for inhibitors of drug-seeking behavior, including the anti-epileptic carbamazepine, the tran- quilizer desipramine, and the analgesic buprenorphine. Clinical trials are in preparation or in progress for each. Other promising agents are under consideration for trial, but pharmaceutical companies may not undertake them unless they foresee a large market for the developed product. Thus, a national commitment to pay for effective therapy would unleash a massive commercial development effort. What must be done? Outstanding scientists must be recruited to this area of investigation. To achieve this goal, addiction research must be identified by the government as a national research priority. It requires participation from clinical investigators other than psychiatrists and psychologists, including pediatricians and internists. It involves broadly advertising the availability of funds and the excitement and importance of this research. After all, deciphering tolerance and reinforcement might generate a Nobel Prize. To that end, the University of California, Los Angeles, and National Institute on Drug Abuse recently cosponsored a sophisticated scientific conference on the biology of addiction to define current knowledge, establish communication between investigators in different areas, and induce young scientists into the field. There is also a great need for a private, nonprofit foundation for the biological study of addiction, to engage public interest, supplement government funding, provide educational materials, and lobby Congress for federal support. Addiction reversal offers the best and perhaps the most cost-effective approach to the drug epidemic. If successful, the hooked would regain the opportunity to live a fruitful life. Effective therapy would be widely available as it would become part of the medical mainstream. As the reservoir of substance abusers declined, so would the profitability of trading in drugs. Ultimately, society would be spared vast expenditures for interdiction, law enforcement, and health care. The drug-induced unraveling of our social fabric and the loss of our competitiveness would be reversed. We should lead with science and technology, our greatest strengths in responding to the epidemic of substance abuse. The laboratory must be a principal battleground for a successful "war on drugs." Stanley Korenman is professor of medicine and associate dean for educational development at the UCLA School of Medicine.

Battle Against Drug Addiction Must Be Waged From Better Financed Laboratories

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